US3109019A - Process for preparing a water-soluble sodium salt of acetylsalicylic acid - Google Patents
Process for preparing a water-soluble sodium salt of acetylsalicylic acid Download PDFInfo
- Publication number
- US3109019A US3109019A US820603A US82060359A US3109019A US 3109019 A US3109019 A US 3109019A US 820603 A US820603 A US 820603A US 82060359 A US82060359 A US 82060359A US 3109019 A US3109019 A US 3109019A
- Authority
- US
- United States
- Prior art keywords
- water
- acetylsalicylic acid
- preparing
- sodium salt
- soluble sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims description 15
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 title description 14
- 159000000000 sodium salts Chemical class 0.000 title description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000007795 chemical reaction product Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 150000007514 bases Chemical class 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- NOJNFULGOQGBKB-UHFFFAOYSA-M sodium;3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxypyridin-3-yl)phenyl]methyl]-5-[(5-methylpyridin-2-yl)methoxy]indol-2-yl]-2,2-dimethylpropanoate Chemical compound [Na+].C1=NC(OCC)=CC=C1C(C=C1)=CC=C1CN1C2=CC=C(OCC=3N=CC(C)=CC=3)C=C2C(SC(C)(C)C)=C1CC(C)(C)C([O-])=O NOJNFULGOQGBKB-UHFFFAOYSA-M 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- JZLOKWGVGHYBKD-UHFFFAOYSA-M sodium;2-acetyloxybenzoate Chemical compound [Na+].CC(=O)OC1=CC=CC=C1C([O-])=O JZLOKWGVGHYBKD-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
Definitions
- acetylsalicylic acid Since about 60 years the acetylsalicylic acid has been used as an important chemotherapeutically active agent on a large scale, particularly as a valuable analgesic agent and in the treatment of rheumatic disorders. Due to its low solubility in water, it has been administered in the form of solid tablets per os, in numerous cases in combination with other medicaments.
- Acetylsalicylic acid is reacted with NaHCO or Na CO or their mixtures in solid condition, in the presence of a limited, small amount of water which is sutficient for moistening the beforementioned reaction components and the salt-forming reaction is conducted by mild heating of the reaction mass, whereby the water for-med in the reaction keeps the reaction going with the formation of a solid reaction product.
- This reaction product is cautiously dried, if desired after subjecting the reaction product to pressing or centrifuging prior to drying.
- the sodium salts of acetylsalicylic acid are easily soluble in cold or warm Water, of, for example, -40 C.
- the salts prepared according to this invention are practically stable in dry condition.
- Example 1 180 grams of acetylsalicylic acid are uniformly moistened with about 25 grams of Water and mixed during about 10-15 minutes with about 100 grams of NaHCO
- the formation of the sodium salt starts at ordinary room temperature, erg. -20 C., with the evolution of gaseous CO and lowering of temperature.
- the reaction mass is heated up to about 30 C., whereby the mass first becomes temporarily liquid and then solidifies with the formation of crystals. Completion of the reaction is indicated when a sample of the mass dissolves in water without substantial evolution of CO This completion takes about 60 to 90 minutes.
- the reaction mass is allowed to cool, is disintegrated and then dried, if desired after pressing or centrifuging.
- the drying temperature 3,109,019 Patented Oct. 29, 1963 should not exceed 50-52 C.
- The-salt obtained has a pleasant acidulous taste in solid condition. It 1s easily and quickly soluble in water to a tasteless clear solution.
- Example 2 grams of acetylsalicylic acid, 25 grams of water, and 168 grams of NaHCO are treated in the manner described in the above Example 1, whereby 286 grams of solid product consisting of 1 mol of. acetylsalicylic acid sodiumsalt and 1 mol of NaHOG are obtained.
- Example 3 In carrying out the above Example 1 or 2, the acetylsalicylic acid and the NaHCO are mixed in the absence of water, which is then added to the mixture in the amount stated in the above Example 1 or 2.
- Example 4 The ingredients described in the above Examples 1 and 2 are mixed and stirred in dry condition and warmed on a water bath to about 35 C. To this mixture 15-20 gramspreferably 18 gramswater of 35 C. are at once added. After the temperature falls to about 25 C., the mixture is kept at about 30 C. until a small sample dissolves in water easily and substantially without the evolution of CO in cold water. The resulting mass is dried and is then free from salicylic acid.
- Example 5 In the above examples the sodium bicarbonate is partly or entirely substituted by an equivalent amount of sodium carbonate and the process is carried out in the manner described in any of the preceding examples.
- a process for preparing a water-soluble sodium salt of acetylsalicylic acid comprising reacting in the range between ordinary room temperature and 35 C., acetylsalicylic acid and a basic compound in solid condition selected from the group consisting of NaHCO and Na CO in the presence of, as the sole added liquid, a limited amount of water which is suiiicient only for moistening the reactants, and drying the reaction product at a temperature not exceeding 50 C.
Description
United States Patent $102019 PRQCESS EGR PREPARENG A WATER-SOLUBLE SGDTUM SALT (PF ACETYLSALICYLIC AGED Peter Schliisser, Braheclrstrasse 16, Letmathe, Westphalia, Germany No Drawing. Filed June 16, 1959, Ser. No. 820,603 6 Claims. (Cl. 260-480) This invention relates to the preparation of watersoluble salts from acetylsalicylic acid and it has particular relation to the preparation of water-soluble salts of the acetylsalicylic acid with sodium.
Since about 60 years the acetylsalicylic acid has been used as an important chemotherapeutically active agent on a large scale, particularly as a valuable analgesic agent and in the treatment of rheumatic disorders. Due to its low solubility in water, it has been administered in the form of solid tablets per os, in numerous cases in combination with other medicaments.
Many attempts have been made to react the acetylsalicylic acid with salt-forming ingredients in the presence of organic solvents in order to convert it into easily water-soluble salts and it also has been suggested to mix the acetylsalicylic acid in the absence of water with oxides, hydroxides or carbonates of metals in order to form products to be mixed with water just before therapeutic administration. The normal way of forming salts in aqueous medium could not be used in the case of acetyl salicylic acid in view of the decomposition of the acetyl salicylic acid by saponification in aqueous medium.
It has now been unexpectedly found that water-soluble salts of acetylsalicylic acid which are practically free from saponification products, such as salicylic acid and acetic acid, can be formed by proceeding in the following manner.
Acetylsalicylic acid is reacted with NaHCO or Na CO or their mixtures in solid condition, in the presence of a limited, small amount of water which is sutficient for moistening the beforementioned reaction components and the salt-forming reaction is conducted by mild heating of the reaction mass, whereby the water for-med in the reaction keeps the reaction going with the formation of a solid reaction product. This reaction product is cautiously dried, if desired after subjecting the reaction product to pressing or centrifuging prior to drying.
The sodium salts of acetylsalicylic acid are easily soluble in cold or warm Water, of, for example, -40 C. The salts prepared according to this invention are practically stable in dry condition.
The following examples illustrate some specific embodiments of and best modes for carrying out the invention to which the invention is not limited.
Example 1 180 grams of acetylsalicylic acid are uniformly moistened with about 25 grams of Water and mixed during about 10-15 minutes with about 100 grams of NaHCO The formation of the sodium salt starts at ordinary room temperature, erg. -20 C., with the evolution of gaseous CO and lowering of temperature. The reaction mass is heated up to about 30 C., whereby the mass first becomes temporarily liquid and then solidifies with the formation of crystals. Completion of the reaction is indicated when a sample of the mass dissolves in water without substantial evolution of CO This completion takes about 60 to 90 minutes. The reaction mass is allowed to cool, is disintegrated and then dried, if desired after pressing or centrifuging. The drying temperature 3,109,019 Patented Oct. 29, 1963 should not exceed 50-52 C. The-salt obtained has a pleasant acidulous taste in solid condition. It 1s easily and quickly soluble in water to a tasteless clear solution.
Example 2 grams of acetylsalicylic acid, 25 grams of water, and 168 grams of NaHCO are treated in the manner described in the above Example 1, whereby 286 grams of solid product consisting of 1 mol of. acetylsalicylic acid sodiumsalt and 1 mol of NaHOG are obtained.
Example 3 In carrying out the above Example 1 or 2, the acetylsalicylic acid and the NaHCO are mixed in the absence of water, which is then added to the mixture in the amount stated in the above Example 1 or 2.
The mixture of acetylsalicylic acid, NaHCO and water is then iurther treated in the manner described in the above Example 1.
Example 4 The ingredients described in the above Examples 1 and 2 are mixed and stirred in dry condition and warmed on a water bath to about 35 C. To this mixture 15-20 gramspreferably 18 gramswater of 35 C. are at once added. After the temperature falls to about 25 C., the mixture is kept at about 30 C. until a small sample dissolves in water easily and substantially without the evolution of CO in cold water. The resulting mass is dried and is then free from salicylic acid.
Example 5 In the above examples the sodium bicarbonate is partly or entirely substituted by an equivalent amount of sodium carbonate and the process is carried out in the manner described in any of the preceding examples.
What is claimed is:
1. A process for preparing a water-soluble sodium salt of acetylsalicylic acid, comprising reacting in the range between ordinary room temperature and 35 C., acetylsalicylic acid and a basic compound in solid condition selected from the group consisting of NaHCO and Na CO in the presence of, as the sole added liquid, a limited amount of water which is suiiicient only for moistening the reactants, and drying the reaction product at a temperature not exceeding 50 C.
2. A process as claimed in claim 1, in which water is mechanically removed from the reaction mass, prior to drying.
3. A process as claimed in claim 1, in which the reactants are used in about stoichiometric proportions.
4. A process as claimed in claim 1, in which the basic compound is sodium bicarbonate.
5. A process as claimed in claim 4, in which the sobicarbonate is used in an excess of the one mol.
6. A process as claimed in claim 1, in which a mixture of NaHCO and Na CO is used as the basic compound.
References Cited in the file of this patent UNITED STATES PATENTS 1,113,742 Berendes et al. Oct. 13, 1914 1,129,953 Busch Mar. 2, 1915 1,217,862 Gerngross Feb. 27, 1917 1,225,407 Bush et al. May 8, 1917 1,486,373 Gerngross et al. 11, 1924 2,003,374 Lawrence June 9, 1935 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 I0) ,019 02 Labor 29, 1963 Peter Schl'sser rs in the above numbered etters Patent should read as rtified that error appea pat- It is hereby ce tion and that the said L ant requiring correc corrected below.
Column 2, line 57 Signed and sealed thi strike out "the".
s 21st day of April 1964.
(SEAL) EDWARD J. BRENNER ERNEST W SWIDER Commissioner of Patents Attesting Officer
Claims (1)
1. A PROCESS FOR PREPARING A WATER-SOLUBLE SODIUM SALT OF ACETYLSALICYCLIC ACID, COMPRISING REACTING IN THE RANGE BETWEEN ORDINARY ROOM TEMPERATURE AND 35*C., ACETYLSALICYCLIC ACID AND A BASIC COMPOUND INSOLID CONDITION SELECTED FROM THE GROUP CONSISTING OF NAHCO3 AND NA2CO3, IN THE PRESENCE OF, AS THE SOLE ADDED LIQUID, A LIMITED AMOUNT OF WATER WHICH IS SUFFICIENT ONLY FOR MOISTENING THE RACTANTS, AND DRYING THE REACTION PRODUCT AT A TEMPERATURE NOT EXCEEDING 50*C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US820603A US3109019A (en) | 1959-06-16 | 1959-06-16 | Process for preparing a water-soluble sodium salt of acetylsalicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US820603A US3109019A (en) | 1959-06-16 | 1959-06-16 | Process for preparing a water-soluble sodium salt of acetylsalicylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3109019A true US3109019A (en) | 1963-10-29 |
Family
ID=25231268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US820603A Expired - Lifetime US3109019A (en) | 1959-06-16 | 1959-06-16 | Process for preparing a water-soluble sodium salt of acetylsalicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3109019A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3985792A (en) * | 1971-12-23 | 1976-10-12 | Alexander Galat | Stable sodium acetylsalicylate and method for its manufacture |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1113742A (en) * | 1914-01-05 | 1914-10-13 | Synthetic Patents Co Inc | Magnesium salts of acylated aromatic ortho-oxycarboxylic acids. |
| US1129953A (en) * | 1914-02-25 | 1915-03-02 | Firm Of Johann A Wuelfing | Process of manufacturing lithium acetylsalicylate. |
| US1217862A (en) * | 1912-12-04 | 1917-02-27 | Otto Gerngross | Salts of acetylsalicylic acid and process of manufacture of same. |
| US1225407A (en) * | 1915-06-09 | 1917-05-08 | Firm Of Johann A Wuelfing | Manufacture of calcium acetyl salicylate. |
| US1486373A (en) * | 1913-01-17 | 1924-03-11 | Chemical Foundation Inc | Composition of matter to be used for the manufacture of salts of acetyl-salicylic acid |
| US2003374A (en) * | 1932-07-21 | 1935-06-04 | Lee Lab Inc | Preparation of calcium acetylsalicylate |
-
1959
- 1959-06-16 US US820603A patent/US3109019A/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1217862A (en) * | 1912-12-04 | 1917-02-27 | Otto Gerngross | Salts of acetylsalicylic acid and process of manufacture of same. |
| US1486373A (en) * | 1913-01-17 | 1924-03-11 | Chemical Foundation Inc | Composition of matter to be used for the manufacture of salts of acetyl-salicylic acid |
| US1113742A (en) * | 1914-01-05 | 1914-10-13 | Synthetic Patents Co Inc | Magnesium salts of acylated aromatic ortho-oxycarboxylic acids. |
| US1129953A (en) * | 1914-02-25 | 1915-03-02 | Firm Of Johann A Wuelfing | Process of manufacturing lithium acetylsalicylate. |
| US1225407A (en) * | 1915-06-09 | 1917-05-08 | Firm Of Johann A Wuelfing | Manufacture of calcium acetyl salicylate. |
| US2003374A (en) * | 1932-07-21 | 1935-06-04 | Lee Lab Inc | Preparation of calcium acetylsalicylate |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3985792A (en) * | 1971-12-23 | 1976-10-12 | Alexander Galat | Stable sodium acetylsalicylate and method for its manufacture |
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